Asthma Primer

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Asthma Primer

• Wayne Kradjan, Pharm. D.

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Definition of Asthma

• A chronic inflammatory disorder of the airways
• In susceptible individuals, this inflammation
  causes episodes of wheezing, breathlessness,
  chest tightness and coughing, particularly at
  night or early morning.
• Usually associated with widespread but variable
  airflow obstruction (bronchospasm) that is often
  reversible, either spontaneously or with
  treatment.
• Inflammation also causes an increase in bronchial
  hyperresponsiveness to a variety of stimuli
  (triggers)

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Large, central airways
Small, peripheralAirways
Only site ofgas exchange
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Causes of Airflow Obstruction

• Bronchospasm- Hyperresponsiveness and narrowing
  of airways (bronchi) due to muscle spasm.
• Airway edema (swelling of walls)
• Mucous plugging
• All made worse by airway inflammation

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Bronchial Hyperresponsiveness

• More easily induced bronchospastic response to a
  variety of stimuli that may not otherwise cause a
  response in the general population.
• Allergens
• Chemicals, irritants
• Exercise
• Response may also be more intense and prolonged
• Non-asthma patients may develop a transient BHR
  after viral upper respiratory infection.

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Asthma Triggers

• Allergens (seasonal/ perennial)
• Grass, weeds, pollen, mold, mildew
• Animal dander, saliva, dust mites
• Chemical irritants and fumes
• Cigarette smoke, pollution, perfume
• Household cleaners, occupational
• Viral infections, rhinitis, sinusitis, (post
  nasal drip)
• Gastroesophageal reflux (GERD)
• Exercise cold, dry air
• Extreme emotions
• Drugs (aspirin, beta blockers)

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Measuring Airflow Obstruction

• Assessing air outflow
• Peak flow Maximum rate (L/min) of airflow out
  of the lung during a forced exhalation.
• FEV1 Forced expiratory volume in one second.
  Actual volume (L) of air expired in the first
  second of a forced exhalation.
• FVC Forced vital capacity. Total volume of air
  expired during a forced exhalation.

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Peak Flow Meter
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Obstructive Airways Disease Sequence of Events
Inflammation, nerve exposure
Hyperresponsiveness
Trigger allergen or irritant exposure(cold
air, exercise)
Bronchospasm (? FEV1, peak flow)mucous, edema,
cough
OBSTRUCTION
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Epidemiology

• 5 of US population
• 5,000 deaths per year in US
• Higher incidence in inner city, especially
  African Americans and Hispanic populations.
• Racial vs. socioeconomic?

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Environmental Factors

• Increased time spent indoors
• Indoor allergens (molds, mites, cockroaches)
• Tobacco smoke exposure
• maternal smoking risk for child
• Increased childhood infections associated with
  lower risk
• Having older or multiple siblings or day care
  center attendance may lower risk (more childhood
  infection)
• Hygienic hypothesis

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Childhood onset

• Most common chronic disease of children (6.9 of
  population)
• More likely to be allergic basis
• Common child with positive family history of
  asthma and allergy to tree and grass pollen,
  house dust mites, household pets and molds.
• 30-70 markedly improve or symptom free as adult

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Adult onset

• May be allergic or non-allergic
• Often negative family history and negative skin
  tests to common allergens
• Often history of nasal polyps, aspirin
  sensitivity and chronic sinusitis
• Environmental exposure wood dust, chemicals,
  pollutants at workplace or in air
• Chemical sensitizers viral infection, tobacco
  smoke, diet, perfume

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Expert Panel 2 Report
Guidelines for the Diagnosis and Management of
Asthma NIH Publication 97-4051A National
Institutes of Health.National Heart, Lung and
Blood InstituteMay 1997 http//www.nhlbi.nih.gov
/guidelines/index.htm Schering, Astra-Zeneca,
or Glaxo-Wellcome
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Update on Selected Topics 2002
Guidelines for the Diagnosis and Management of
Asthma NIH Publication 02-5075 National
Institutes of Health.National Heart, Lung and
Blood InstituteNovember 2002 http//www.nhlbi.ni
h.gov/guidelines/asthma/asthsumm.htm J Allergy
Clin Immunol. 2002110S1-S219 (Nov supplement)
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Step Approach to Classification

• Mild Intermittent
• Sxs lt2/week, PM sxs lt 2/month
• PFTs gt80, lt 20 variability
• Mild Persistent
• Sxs 3-6x/ week PM sxs 3-4/month
• PFTs gt80, 20-30 variability
• Moderate Persistent
• Sxs daily PM sxs gt 5 per/month
• PFTs 60-80, gt30 variability
• Severe Persistent
• Sxs continual PM sxs frequent
• PFTs lt60, gt30 variability
• Acute exacerbations

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StagingFurther Considerations

• Seasonality
• Nocturnal symptoms
• Exercise induced
• Peak flow monitoring
• Daily fluctuations
• Cough variant
• Wheezy bronchitis in children

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Reliever, Rescue Drugs

• Rapid acting bronchodilators
• beta adrenergic agonists
• intermediate duration (3-6 hrs)
• Often called short acting
• metered dose inhaler (MDI),dry powder inhaler
  (DPI, breath actuated),solution for nebulization
• Albuterol (salbutamol) (Proventil, Ventolin)
• Levalbuterol (Xopenex)
• Bitolterol (Tornalate)
• Metaproterenol (Alupent, Metaprel)
• Pirbuterol (Maxair)
• Terbutaline (Bricanyl, Brethine)
• (Epinephrine, isoproterenol, isoetharine)

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Metered Dose InhalerAlbuterol (Proventil HFA)
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Air Jet Nebulizer
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Anticholinergicbronchodilators

• Ipratropium (Atrovent)Tiotropium (Spiriva)
• MDI (Atrovent and Spiriva)
• Also combination with albuterol Combivent
• Solution for nebulization (Atrovent)
• Also combination with albuterolDuoNeb (500
  mcg/2.5 mg)
• Slower onset, longer acting than albuterol
• Atrovent QID Spiriva QD
• Dry mouth and blurred vision
• Greater role in COPD than in asthma

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Controller DrugsAntiinflammatory

• Inhaled corticosteroids
• Beclomethasone (Beclovent, Vanceril)
• Budesonide (Pulmicort)(Turbuhaler, and Respules)
• Flunisolide (Aerobid, Aerobid M)
• Fluticasone (Flovent)(Advair combo with
  salmeterol)
• Triamcinolone (Azmacort)
• Important to note
• Low, intermediate, high dose
• dosage form and strengths

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Non-Steroid ControllersAntiinflammatory

• Mast cell stabilizers(inhaled MDI or nebs)
• Cromolyn (Intal)
• Nedocromil (Tilade)
• Leukotriene modifiers(Oral)
• Lipooxygenase inhibitor
• Zileuton (Zyflo)
• Receptor blockers
• Zafirlukast (Accolate)
• Montelukast (Singulair)

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Long acting bronchodilators

• Inhaled beta agonist
• Salmeterol (Serevent MDI and Diskus)
• Formoterol (Foradil Aerolizer)
• Night time, exercise or adjunct to
  anti-inflammatory drugs
• Oral beta adrenergic agonists
• albuterol, metaproterenol, terbutaline
• sustained release for night timeProventil
  Repetabs, Volmax
• syrups for children (albuterol, metaproterenol

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Salmeterol (Serevent) Diskus50 mcg/dose 60 doses
Open door toreveal mouthpiece
Slide lever. Click indicates dose in
place.Dose counter advances.
Hold level to holdpowder in place.Inhale
quickly.Close door to reset.
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Long acting bronchodilators (continued)

• Theophylline
• rapid acting, sustained release(many products
  recently removed from the market)
• intravenous (aminophylline)
• Possibly mild anti-inflammatory
• Increased diaphragm contractility(diaphragmatic
  inotrope)
• Primarily reserved for COPD

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Other asthma medications

• Oral or injectable steroids
• Prednisone, prednisolone, methylprednisolone
• burst therapy for rapid decline
• Emergency and hospital use
• Methotrexate
• Allergy desensitization
• Soluble IL-4 receptor (IL4R) to bind IL-4 and
  prevent binding of IL-4 to tissue receptors. 3
  mg Q week via inhalation
• Olizumab recombinant monoclonal antibody to IgE
  150-300 mg SC Q 2- 4 weeks

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Therapeutic goalsIndividualize to patient

• Minimal, infrequent episodes
• Freedom from symptomsDay and night.
• Maintain normal activity including exercise
• Maintain best possible pulmonary function
• Consider what is realistic
• Prevent acute episodes
• lt 3 beta agonist per week
• No emergency room visits or hospitalizations.

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Therapeutic goals (cont.)

• Avoid medication adverse effects
• Prevent asthma related death
• Meet patient/family expectations
• Patient/family education
• symptoms
• triggers
• metered dose inhaler technique(have patient
  demonstrate)
• reliever vs controller drugs
• peak flow meter monitoring(Green, yellow and red
  zones)

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Environmental Control

• Same as for allergic rhinitis
• Bedding
• Carpets
• Stuffed animals
• Pets
• Avoidance of allergens and triggers

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Step Approach to Classification and Therapy

• Mild Intermittent
• PRN bronchodilators
• Mild Persistent
• Symptoms 3-6 times/ week
• Add antiinflammatory
• Moderate Persistent
• Combinations of antiinflammatories and long
  acting bronchodilators
• Severe Persistent
• Acute exacerbations

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StagingFurther Considerations

• Seasonality
• Nocturnal symptoms
• Exercise induced
• Peak flow monitoring
• Daily fluctuations
• Cough variant
• Wheezy bronchitis in children

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COPD Chronic Obstructive Pulmonary Disease

• Any lung condition causing longstanding airflow
  limitation with impaired expiratory outflow
• airflow obstruction due to chronic bronchitis
  (and/or) emphysema
• Generally progressive, may be accompanied by
  airway hyperreactivity, and may be partially
  reversible
• caused by abnormal inflammatory reaction to
  chronic inhalation of particles
• 2-10 of US population over age 554th to 5th
  leading cause of death

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Assessing Peak Flow Rate
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Pulmonary functionBronchodilator tone

• Peak expiratory flow rate (PEFR) in liters/
  minute
• Forced expiratory volume in one second (FEV1) in
  liters
• Normal values vary according to sex, age, height
• Reported as absolute values or
• Percentage of normal or of personal best
• Establish patient zones
• Green 80-100 of normal
• Yellow 50-79 of normal
• Red lt50 of normal

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Peak Expiratory Flow Rate

• First blast of air exhaled by the patient reaches
  this flow rate almost immediately.
• The flow rate quickly slows as more air is
  exhaled.
• Less elastic recoil by lung
• Indirect measure of lumen size of large airways
  and strength of expiratory muscles during maximal
  effort.

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True Zone Peak Flow Meter
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Peak Flow Meter
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Directions for use of Peak Flow Meter

• zero the pointer
• Move indicator to bottom of numbered scale on
  meter.
• Stand upright
• Breathe in as deeply and completely as possible
• Close lips around mouthpiece to form tight seal
• Do not put tongue in opening
• Quickly blow out as hard and fast as you can.
• Note reading repeat 3 times